P46460 (NSF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vesicle-fusing ATPase
EC=3.6.4.6

Alternative name(s):
N-ethylmaleimide-sensitive fusion protein
Short name=NEM-sensitive fusion protein
Suppressor of K(+) transport growth defect 2
Short name=Protein SKD2
Vesicular-fusion protein NSF

Gene names

Name:	Nsf
Synonyms:	Skd2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	744 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seem to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack GRIA2 leads to influence GRIA2 membrane cycling By similarity. Ref.6
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Binds 1 magnesium ion per subunit By similarity.
Subunit structure	Homohexamer. Interacts with GABARAP and GABARAPL2. Interacts with GRIA2. Interacts with PLK2, leading to disrupt the interaction with GRIA2. Interacts with MUSK; may regulate MUSK endocytosis and activity By similarity. Interacts with CDK16. Ref.6 Ref.7
Subcellular location	Cytoplasm.
Post-translational modification	Phosphorylation at Ser-569 interferes with homohexamerization.
Sequence similarities	Belongs to the AAA ATPase family.
Sequence caution	The sequence CAM20943.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAM23742.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of receptor recycling Inferred from electronic annotation. Source: Compara potassium ion transport Inferred from direct assay Ref.1. Source: MGI protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity, coupled Inferred from mutant phenotype PubMed 12832401. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW syntaxin binding Inferred from direct assay PubMed 14755058. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dlg4	Q62108	4	EBI-398006,EBI-300895
Lrrk2	Q5S006	2	EBI-398006,EBI-2693710
Musk	Q61006-3	5	EBI-398006,EBI-6308424

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 744	744	Vesicle-fusing ATPase		PRO_0000084564
Regions
	Nucleotide binding	505 – 510	6	ATP By similarity
	Nucleotide binding	545 – 552	8	ATP By similarity
Sites
	Metal binding	550	1	Magnesium
Amino acid modifications
	Modified residue	259	1	Phosphotyrosine Ref.8
	Modified residue	569	1	Phosphoserine; by CDK16 Ref.6
Experimental info
	Mutagenesis	569	1	S → A: Abolishes phosphorylation by CDK16. Ref.6
	Mutagenesis	569	1	S → E: Interferes with oligomerization. Ref.6
	Sequence conflict	300	1	A → G in BAC39361. Ref.2
	Sequence conflict	316 – 326	11	LGANSGLHIII → VCGHKTNLLKM in BAC34637. Ref.2
	Sequence conflict	492	1	F → I in AAA50498. Ref.1
	Sequence conflict	552	1	L → V in AAA50498. Ref.1
	Sequence conflict	657	1	M → I in BAC25937. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P46460 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: BE55AD0056AD5585	FASTA	744	82,613
	10 20 30 40 50 60 MAGRTMQAAR CPTDELSLSN CAVVNEKDFQ SGQHVMVRTS PNHKYIFTLR THPSVVPGCI 70 80 90 100 110 120 AFSLPQRKWA GLSIGQDIEV ALYSFDKAKQ CIGTMTIEID FLQKKNIDSN PYDTDKMAAE 130 140 150 160 170 180 FIQQFNNQAF SVGQQLVFSF NDKLFGLLVK DIEAMDPSIL KGEPASGKRQ KIEVGLVVGN 190 200 210 220 230 240 SQVAFEKAEN SSLNLIGKAK TKENRQSIIN PDWNFEKMGI GGLDKEFSDI FRRAFASRVF 250 260 270 280 290 300 PPEIVEQMGC KHVKGILLYG PPGCGKTLLA RQIGKMLNAR EPKVVNGPEI LNKYVGESEA 310 320 330 340 350 360 NIRKLFADAE EEQRRLGANS GLHIIIFDEI DAICKQRGSM AGSTGVHDTV VNQLLSKIDG 370 380 390 400 410 420 VEQLNNILVI GMTNRPDLID EALLRPGRLE VKMEIGLPDE KGRLQILHIH TARMRGHQLL 430 440 450 460 470 480 SADVDIKELA VETKNFSGAE LEGLVRAAQS TAMNRHIKAS TKVEVDMEKA ESLQVTRGDF 490 500 510 520 530 540 LASLENDIKP AFGTNQEDYA SYIMNGIIKW GDPVTRVLDD GELLVQQTKN SDRTPLVSVL 550 560 570 580 590 600 LEGPPHSGKT ALAAKIAEES NFPFIKICSP DKMIGFSETA KCQAMKKIFD DAYKSQLSCV 610 620 630 640 650 660 VVDDIERLLD YVPIGPRFSN LVLQALLVLL KKAPPQGRKL LIIGTTSRKD VLQEMEMLNA 670 680 690 700 710 720 FSTTIHVPNI ATGEQLLEAL ELLGNFKDKE RTTIAQQVKG KKVWIGIKKL LMLIEMSLQM 730 740 DPEYRVRKFL ALMREEGASP LDFD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel mammalian member of the NSF/CDC48p/Pas1p/TBP-1 family through heterologous expression in yeast." Perier F., Coulter K.L., Liang H., Radeke C.M., Gaber R.F., Vandenberg C.A. FEBS Lett. 351:286-290(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Head, Lung, Medulla oblongata, Spinal ganglion and Thymus.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Eye and Mammary tumor.
[5]	Lubec G., Kang S.U., Klug S., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 45-50; 69-87; 106-116; 151-161; 170-198; 218-232; 255-266; 294-303; 305-314; 316-335; 338-357; 404-413; 416-427; 435-446; 517-529; 534-559; 573-581; 595-631; 640-648 AND 710-725, MASS SPECTROMETRY. Strain: C57BL/6 and OF1. Tissue: Brain and Hippocampus.
[6]	"Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications in the regulation of its hexamerization and exocytosis." Liu Y., Cheng K., Gong K., Fu A.K., Ip N.Y. J. Biol. Chem. 281:9852-9858(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDK16, SUBUNIT, MUTAGENESIS OF SER-569, PHOSPHORYLATION AT SER-569.
[7]	"Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine receptor clustering in response to agrin." Zhu D., Yang Z., Luo Z., Luo S., Xiong W.C., Mei L. J. Neurosci. 28:1688-1696(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MUSK.
[8]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-259, MASS SPECTROMETRY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U10120 mRNA. Translation: AAA50498.1. AK028415 mRNA. Translation: BAC25937.1. AK032120 mRNA. Translation: BAC27713.1. AK049281 mRNA. Translation: BAC33656.1. AK051430 mRNA. Translation: BAC34637.1. AK085086 mRNA. Translation: BAC39361.1. AK153905 mRNA. Translation: BAE32247.1. AL596108, AL603829 Genomic DNA. Translation: CAM20943.1. Sequence problems. AL596108, AL603829 Genomic DNA. Translation: CAM20945.1. AL603829, AL596108 Genomic DNA. Translation: CAM23742.1. Sequence problems. AL603829, AL596108 Genomic DNA. Translation: CAM23743.1. BC006627 mRNA. Translation: AAH06627.1. BC019167 mRNA. Translation: AAH19167.1.
IPI	IPI00656325.
RefSeq	NP_032766.2. NM_008740.4.
UniGene	Mm.260117. Mm.474887.
3D structure databases
ProteinModelPortal	P46460.
SMR	P46460. Positions 1-201, 220-742.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46460. 12 interactions.
MINT	MINT-89339.
PTM databases
PhosphoSite	P46460.
2D gel databases
REPRODUCTION-2DPAGE	P46460.
Proteomic databases
PaxDb	P46460.
PRIDE	P46460.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000103075; ENSMUSP00000099364; ENSMUSG00000034187.
GeneID	18195.
KEGG	mmu:18195.
UCSC	uc007lvt.1. mouse.
Organism-specific databases
CTD	4905.
MGI	MGI:104560. Nsf.
Phylogenomic databases
eggNOG	COG0464.
GeneTree	ENSGT00530000064085.
HOVERGEN	HBG000324.
InParanoid	P46460.
KO	K06027.
OMA	IFTLRTH.
OrthoDB	EOG4DZ1TR.
Gene expression databases
ArrayExpress	P46460.
Bgee	P46460.
CleanEx	MM_NSF.
Genevestigator	P46460.
GermOnline	ENSMUSG00000034187. Mus musculus.
Family and domain databases
Gene3D	2.40.40.20. 1 hit.
InterPro	IPR003593. AAA+_ATPase. IPR009010. Asp_de-COase-like_dom. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR004201. Cdc48_dom2. IPR003338. CDC4_N-term_subdom. [Graphical view]
Pfam	PF00004. AAA. 2 hits. PF02933. CDC48_2. 1 hit. PF02359. CDC48_N. 1 hit. [Graphical view]
SMART	SM00382. AAA. 2 hits. SM01072. CDC48_2. 1 hit. SM01073. CDC48_N. 1 hit. [Graphical view]
SUPFAM	SSF50692. Asp_decarb_fold. 1 hit.
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NSF. mouse.
NextBio	293548.
SOURCE	Search...

Entry information

Entry name

NSF_MOUSE

Accession

Primary (citable) accession number: P46460
Secondary accession number(s): A2A646 , Q8BQ65, Q8C3R2, Q8CCT9, Q8CEF0, Q923C6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program